Department of Biochemistry, Mymensingh Medical College, Mymensingh, Bangladesh
Background and objectives: Alteration of
magnesium (Mg) and copper (Cu) concentrations in blood has been observed in
normal pregnancy as well as in gestational diabetes mellitus (GDM). The present
study was aimed to evaluate the serum Mg and Cu levels in Bangladeshi women with
GDM in their second and third trimester of pregnancy.
Methods: The study was conducted at Mymensingh Medical
College Hospital from July 2013 to June 2014. Pregnant women, in their second
and third trimester, attending the outpatient department of Obstetrics and
Gynecology and the Department of Endocrinology of Mymensingh Medical College
Hospital were enrolled by purposive sampling technique. GDM was diagnosed on
the basis of oral glucose tolerance test (OGTT) as defined in WHO criteria
2013. Blood glucose was estimated by enzymatic GOD-PAP colorimetric method. The
cut off value for fasting plasma glucose level was ≥6.1 mmol/L or ≥7.8 mmol/L 2
hours after glucose load. Serum Cu was
estimated by 3, 5-DiBr-PAESA method and Mg by Xylidyl Blue-I Method as per
Results: A total of 172 pregnant women in their second
and third trimester were enrolled. Out of 172 participants, 86 had GDM and 86
were normoglycemic (control). The mean age of GDM and control groups was
28.6±3.2 years and 27.3±3.1 years respectively. The BMI was 26.4±1.5 m/kg2
and 26.3±1.3 m/kg2. Serum Mg level was significantly low (p<
0.001) in 2nd and 3rd trimesters in GDM cases (1.39±0.26
mg/dl and 0.93±0.15 mg/dl) compared to control group (1.67±0.3 mg/dl and
1.67±0.31mg/dl). On the contrary, serum Cu levels in GDM cases were
significantly (p<0.002) higher in both trimesters (224±333.8 µg/dl and
243.91±6.89 µg/dl) compared to those without GDM (220.1±7.6 µg/dl and 234.9±4.6
µg/dl). There was significant (p<0.001) increase of serum Cu levels in 3rd
trimester compared to 2nd trimester in both GDM and non GDM cases.
Conclusion: There was distinct alteration of serum Mg and
Cu levels in GDM compared to normal pregnancy.
IMC J Med
Sci 2017; 11(1): 25-28
Address for Correspondence: Dr. Farzana Akonjee Mishu, Assistant Professor, Department of
Physiology and Molecular Biology, BIRDEM General Hospital, 122 Kazi Nazrul
Islam Avenue, Dhaka, Bangladesh. Email: firstname.lastname@example.org
diabetes mellitus is defined as carbohydrate intolerance resulting in
hyperglycemia, with first onset or detection during pregnancy [1,2]. Usually initiation of
GDM is in middle and late gestational period and continues to term . Glucose
intolerance usually returns to normal range within six weeks after delivery .
Approximately 1-14 % of all pregnancies are complicated by GDM . The prevalence
of GDM among Bangladeshi pregnant mothers has been reported as 9.7% .
Pregnancy is associated with physiological changes that result in increased
plasma volume and decreased concentrations of plasma proteins and
micronutrients . It is a time of increased nutritional needs, both to
support the rapidly growing fetus and the changes occurring in mother during
pregnancy. Different researchers have demonstrated that macro and micro
nutrients are essential for the optimum development of fetus. Among the
micronutrients, Cu is important, especially early in the life for the
development and maintenance of fetal organs and tissues. Deficiencies of Cu
have been implicated in infertility, pregnancy wastage, congenital
abnormalities, still birth and low birth weight [7,8]. Serum Cu values in healthy
pregnant women increases with gestational period . Serum Cu has been found
to be significantly higher in GDM cases as compared to euglycemic healthy
pregnant women . Earlier studies reported higher level of serum Cu in full
term healthy Bangladeshi pregnant women compared to non pregnant women [11,12].
Likewise, Mg has been found to be linked to fetal and maternal
Mg deficiency during pregnancy is associated with intrauterine growth
retardation and metabolic syndrome in later life of the offspring [13,14]. There is report of low
and variable serum Mg level during second and third trimester of normal pregnancy
. It has been found that serum Mg is depleted at a greater extent in women
with GDM . However, there is no systematic study regarding the serum levels
of Cu and Mg in Bangladeshi pregnant women with GDM. Therefore, the present
study was undertaken to determine the serum Cu and Mg levels in second and
third trimester of pregnancy in Bangladeshi women with GDM.
Materials and Methods
The study was conducted at Mymensingh Medical College
Hospital from July 2013 to June 2014 to evaluate the serum level of magnesium
and copper in pregnant women with GDM. The study protocol was approved by the
institutional review committee and written informed consent was obtained from
all the participants prior to their enrolment into this study.
Study population and
collection of samples:
Pregnant women, in their second and third trimester, attending the outpatient
department of Obstetrics and Gynecology and the Department of Endocrinology of
Mymensingh Medical College Hospital were enrolled by purposive sampling
technique. Pregnant women with the previous history of diabetes, hypertension
and other endocrine disorders were excluded from the study. Data were collected
in a predesigned data collection sheet. The variables included were - age,
height, weight, duration of gestation, family history of diabetes, previous
history of pregnancy and gestational diabetes mellitus. About 5 ml of blood was
collected aseptically with venipuncture from all participants for OGTT and
estimation of serum Cu and Mg levels.
glucose, Cu and Mg:
Blood glucose was estimated by enzymatic GOD-PAP colorimetric method . GDM
was diagnosed on the basis of OGTT as defined in WHO criteria 2013 [1,18]. The
cut off value for fasting plasma glucose level was ≥6.1 mmol/L or ≥7.8 mmol/L 2
hours after glucose load. Serum Cu and Mg were determined by commercial colorimetric
assay kits obtained from Japan
Institute for the Control of Aging (JaICA), Nikken Seal Co., Ltd, Japan. Serum Cu
was estimated by 3, 5-DiBr-PAESA method and Mg by Xylidyl Blue-I Method
as per manufacturer’s instruction.
The results were analyzed and values were expressed as mean
±SD. The level of significance was determined by employing Student’s t test.
A total of 172 pregnant
women in their second and third trimester were enrolled in the study of which 86 had GDM and 86 were normoglycemic by OGTT test. Pregnant women without GDM (normoglycemic) were
considered as control group. The mean age of GDM and control groups were
28.6±3.2 years and 27.3±3.1 years while the
mean BMI was 26.4±1.5 m/kg2 and 26.3±1.3 m/kg2
respectively (Table-1). Serum Mg level was significantly low (p<0.001) in 2nd
and 3rd trimesters in GDM cases (1.4±0.3 mg/dl and 0.9±0.2 mg/dl)
compared to control group (1.7±0.3 mg/dl and 1.7±0.3 mg/dl). The serum Mg level
declined in 3rd trimester compared to 2nd trimester in
GDM cases while there was no such change in cases without GDM. On the contrary,
serum Cu levels in GDM cases were significantly (p<0.002) higher in both
trimesters (224±3.8 µg/dl and 243.9±6.9 µg/dl) compared to those without GDM
(220.1±7.6 µg/dl and 234.9±4.6 µg/dl). There was significant (p<0.01) rise
of serum Cu levels in 3rd trimester compared to 2nd
trimester in both GDM and non GDM cases (Table-2).
Table-1: Age and BMI of study population
Table-2: Serum concentration of Mg and Cu in GDM and euglycemic pregnant women
In this study, we have estimated serum Mg and Cu levels in pregnant
women with GDM and in healthy pregnant women (euglycemic control). Serum Mg concentration
in women with GDM was significantly low compared to that of control.The decrease in serum Mg might be caused by osmotic diuresis and by indirect
hormonal effects. The low serum Mg levels seen in the diabetic population could
be a consequence of insulin resistance and low dietary Mg intake and decreased intestinal
In the present study, the serum concentration of Cu in women
with GDM were significantly higher (p<0.001) compared to the controls.The
possible causes of high serum Cu concentration in GDM cases could be due to the
hormonal, metabolic and enzymatic changes in pregnancy. Increased Cu level in
GDM cases could be due to decreased insulin sensitivity in GDM . Though studies have found increased level of copper in GDM,
others have found no
statistically significant difference of serum Cu concentrations between healthy
pregnant women and women with GDM . However,
pregnant women with GDM should be carefully monitored for adverse effects of
The present study has revealed that there is pronounced
alteration of serum Mg and Cu levels in GDM cases compared to normal pregnancy.
further study should be done to find out the underlying mechanism of alteration
of serum Mg and Cu levels in DGM.
1. Diagnostic criteria and classification of
hyperglycaemia first detected in pregnancy: a World
Health Organization Guideline. Diabetes Res Clin Pract. 2014; 103: 341–3632.
2. Buckley BS, Harreiter J, Damm P, Corcoy R, Chico
A, Simmons D, Vellinga A, et al. Gestational diabetes mellitus in Europe:
prevalence, current screening practice and barriers to screening. A review.
Diabet Med. 2012: 29(7): 844-54. doi:
A, Bagis T, Killicadag EB, Tarim E, Guvener N. Comparison of the criteria for
gestational diabetes mellitus by NDDG and Carpenter and Coustan, and the
outcomes of pregnancy. J Endocrinol Invest. 2002; 25: 357-61.
4. Kim C, Newton KM, Knopp RH. Gestational diabetes
and the incidence of type 2 diabetes. Diabetes Care. 2002; 25: 1862–8.
S, Akhter S, Akashi H, Al-Mamun A, Rahman MA, Islam MM, et al. Screening for
gestational diabetes mellitus and its prevalence in Bangladesh. Diabetes
Res Clin Pract. 2014; 103(1):
6. Ladipo OA. Nutrition in pregnancy: mineral and vitamin
supplements. Am J clin Nutr.
2000; 72: 280-290.
7. Ashworth CJ,
Antipatis C. Micronutrient programming of development throughout gestation. Reproduction
2001; 122(4): 527-535.
8. Keen CL, Uriu-Hare JY, Hawk SN, Jankowski MA, Daston GP,
Kwik-Uribe CL. Effect of copper deficiency on prenatal development and
pregnancy outcome. Am J Clin Nutr.1998; 67(suppl):1003S–1011S.
9. Vukelić J, Kapamadžija A, Petrović D, Grujić
Z, Novakov-Mikić A, Kopitović V, Bjelica A. Variations
of Serum Copper Values in Pregnancy. Srp
Arh Celok Lek.
2012; 140(1-2): 42-46.
10. Asha D, Nanda N, Daniel M, Sen SK, Ranjan T.Association of serum copper level with fasting serum glucose
in south Indian women with gestational diabetes mellitus. Int J Clin Exp Physiol. 2014; 1(4):
11. Sultana M, Jahan N, Sultana N, Ali ML, Sunyal DK, Al Masud MA.
Serum Copper level in Term women. J Dhaka
National Med Coll Hosp. 2011; 17(02): 18-20.
12. Noor N, Jahan N, Sultana N. Serum Copper and Plasma Protein Status
in Normal Pregnancy. J
Bangladesh Soc Physiol. 2012; 7(2): 66-71.
13. Goker TU, Tasdemir N, Kilic S, Abali R, Celik
C, Gulerman HC. Alterations of Ionized and total Magnesium levels in Pregnant
Women with Gestational Diabetes Mellitus. Gynecol
Obstet Invest. 2015; 79: 19-24.
J,Yamato F and Kaneko K. Possible
relationship between low birth weight and magnesium status: from the standpoint
of “foetal origin” hypothesis. Magnesium Res 2006; 19:
15. Baloch GH, Shaikh K, Jaffery MH, Abbas T, Das CM, Devrajan BR, et
al. Serum magnesium level during
pregnancy. World Appl Sci J.
2012; 17(8): 1005-1008.
M, Bardicef O, Sorokin Y, Altura BM, Altura BT, Cotton DB and Resnick LM.
Extracellular and intracellular magnesium depletion in pregnancy and
gestational diabetes. Am J Obstet and Gynecol. 1995; 172(3):1009-1013.
17. Trinder P. Determination of glucose in blood using glucose oxidase with an alternative oxygen
acceptor. Ann.Clin. Biochem 1969; 6: 24-7
Consultation: definition, diagnosis and classification of diabetes mellitus and
its complications: report of a WHO Consultation. Part 1: diagnosis and
classification of diabetes mellitus. Geneva, WHO/NCD/NCS/99. 2:
World Health Organization; 1999.
A, Romem Y, Pelly IZ, Holeberg G, Agam G. Copper metabolism--a factor in
gestational diabetes? Clin chim Acta.